Somatostatin Agonist Pasireotide Inhibits Exercise‐Stimulated Growth in the Male Siberian Hamster (Phodopus sungorus)

Abstract

25The Siberian hamster (Phodopus sungorus) is a seasonal mammal, exhibiting a suite of 26 physiologically and behaviourally distinct traits dependent on the time of year and governed by 27 changes in perceived day length (photoperiod). These attributes include significant weight loss, 28 reduced food intake, gonadal atrophy, and pelage change with short day photoperiod as in winter. 29The central mechanisms driving seasonal phenotype change during winter are mediated by a 30 reduced availability of hypothalamic tri-iodothyronine (T3), but downstream mechanisms 31 responsible for physiological and behavioural changes are yet to be fully elucidated. With access 32 to a running wheel (RW) in short photoperiod, Siberian hamsters which have undergone 33 photoperiod mediated weight loss override photoperiod-drive for reduced body weight and regain 34 weight similar to a hamster held in long days. These changes occur despite retaining the majority 35 of hypothalamic gene expression profiles appropriate for short day hamsters. Utilising the 36 somatostatin agonist pasireotide, we have recently provided evidence for an involvement of the 37 growth hormone axis (GH axis) in the seasonal regulation of bodyweight. In the present study we 38 employed pasireotide to test for the possible involvement of the GH axis in running wheel induced 39 body weight regulation. Pasireotide successfully inhibited exercise stimulated growth in short day 40 hamsters and this was accompanied by altered hypothalamic gene expression of key GH axis 41 components. Our data provides support for an involvement of the GH axis in the RW response in 42Siberian hamsters. 43

An appetite for growth: The role of the hypothalamic – pituitary – growth hormone axis in energy balance

“…This effective reversal of Dehnel's phenomenon has been observed in several seasonal rodent species, and upregulation of the growth axis was implicated in a series of experiments by Katarina Borer and colleagues in the Golden hamster in the 1970s 53 . In our experiments, we recently demonstrated that this exercise stimulated weight gain is associated with increased Ghrh , Npy and Pomc expression in the ARC in Siberian hamsters 50 . The ARC Ghrh expression was unaltered by somatostatin SSTR5 receptor antagonist pasireotide, indicating action downstream of this change in expression, perhaps unsurprising as it is not predicted to cross the blood–brain barrier.…”

“…When given access to a running wheel, the Siberian hamster will spontaneously run for long periods of time during their normally active phase (night), and for hamsters housed in long or short photoperiod they will equally run for 10–15 km per day 50 . Interestingly, this is accompanied with weight gain in short day (or winter) acclimated hamsters, 42,51 probably through increased food intake.…”

“…52 Wheel running stimulated weight gain is accompanied by increased food intake 42,50 and while most of the weight gain is from lean mass there is an almost doubling of fat mass in these hamsters, accompanied by increased circulating insulin. 50 Therefore, this can be considered a poor health response to the wheel running exercise. This effective reversal of Dehnel's phenomenon has been observed in several seasonal rodent species, and upregulation of the growth axis was implicated in a series of experiments by Katarina Borer and colleagues in the Golden hamster in the 1970s.…”

“…When given access to a running wheel, the Siberian hamster will spontaneously run for long periods of time during their normally active phase (night), and for hamsters housed in long or short photoperiod they will equally run for 10-15 km per day. 50 Interestingly, this is accompanied with weight gain in short day (or winter) acclimated F I G U R E 4 Effects of wheel running exercise in Siberian hamsters. Voluntary wheel running in the normally active phase for short photoperiod or winter acclimated Siberian hamsters leads to weight gain and increased food intake.…”

“…This was first demonstrated in the 1990s in castrated male hamsters. 52 Wheel running stimulated weight gain is accompanied by increased food intake 42,50 and while most of the weight gain is from lean mass there is an almost doubling of fat mass in these hamsters, accompanied by increased circulating insulin. 50 Therefore, this can be considered a poor health response to the wheel running exercise.…”